Some early phase clinical studies of candidate HIV cure and remission interventions appear to have adverse medical risk–benefit ratios for participants. Why, then, do people participate? And is it ethically permissible to allow them to participate? Recent work in decision theory sheds light on both of these questions, by casting doubt on the idea that rational individuals prefer choices that maximise expected utility, and therefore by casting doubt on the idea that researchers have an ethical obligation not to enrol participants (...) in studies with high risk–benefit ratios. This work supports the view that researchers should instead defer to the considered preferences of the participants themselves. This essay briefly explains this recent work, and then explores its application to these two questions in more detail. (shrink)

Interest and excitement surround the possibility of developing measures that produce sustained or permanent HIV remission in infected individuals. First-in-human (FIH) trials are one step in exploring this possibility. Initial human trials raise the usual ethical issues associated with human research, and a set of distinct issues. Because the potential direct benefits to FIH trial volunteers will be either small or non-existent, trial risks must be justified by the social value of the information the trials are expected to produce. To (...) minimise and justify risks, researchers must have solid preclinical evidence that FIH trials will be safe and produce information relevant to human health improvements. Researchers must also adopt adequate study safeguards to protect FIH subjects. An ethically defensible study population must be selected as well. (shrink)

Abstract:Therapeutic misconception (TM)—when clinical research participants fail to adequately grasp the difference between participating in a clinical trial and receiving ordinary clinical care—has long been recognized as a significant problem in consent to clinical trials. We suggest that TM does not primarily reflect inadequate disclosure or participants’ incompetence. Instead, TM arises from divergent primary cognitive frames. The researchers’ frame places the clinical trial in the context of scientific designs for assessing intervention efficacy. In contrast, most participants have a cognitive frame (...) that is personal and focused primarily on their medical problems. To illustrate this, we draw on interview material from both clinical researchers and participants in clinical trials. We suggest that reducing TM requires encouraging subjects to adjust their frame, not just add information to their existing frame. What is necessary is ascientific reframingof participation in a clinical trial. (shrink)

Institutional review boards (IRBs) have a reputation for impeding research. This reputation is understandable inasmuch as many studies are poorly designed, exploit participants, or do not ask a relevant question , and it is entirely proper that IRBs should reject such proposals. However, IRBs also frequently reject or tamper with perfectly sound and relevant studies in the name of protecting participants from harm, in accordance with the widely accepted message that “clinical research is justified only when participants are protected from (...) excessive risks”. Here, I argue that IRBs should never reject a study because it poses too high a risk to participants, and that their role should be confined to ensuring that risks and any potential benefits are fully explained to potential participants. Everyone should have the right to participate in research without paternalistic decisions about risk being made on their behalf. (shrink)

It is widely held that individuals who are unable to provide informed consent should be enrolled in clinical research only when the risks are low, or the research offers them the prospect of direct benefit. There is now a rich literature on when the risks of clinical research are low enough to enroll individuals who cannot consent. Much less attention has focused on which benefits of research participation count as ‘direct’, and the few existing accounts disagree over how this crucial (...) concept should be defined. This disagreement raises concern over whether those who cannot consent, including children and adults with severe dementia, are being adequately protected. The present paper attempts to address this concern by considering first what additional protections are needed for these vulnerable individuals. This analysis suggests that the extant definitions of direct benefits either provide insufficient protection for research subjects or pose excessive obstacles to appropriate research. This analysis also points to a modified definition of direct benefits with the potential to avoid these two extremes, protecting individuals who cannot consent without blocking appropriate research. (shrink)

Informed consent is increasingly heralded as an ethical panacea, a tool to counter autocratic and paternalistic medical practices. Debate about the implementation of informed consent is constricted and polarised, centring on the right of individuals to be fully informed and to freely choose versus an autocratic, paternalistic practice that negates individual choice. A bioethical framework, based on a principle-led form of reductive/deductive reasoning, dominates the current model of informed consent. Such a model tends to abstract the process of consent from (...) its clinical and social setting. By fleshing out the social process involved when patients and healthy volunteer subjects consent to take part in clinical drug trials, this paper attempts to address the problem arising from the current ‘empty ethics’ model. My arguments are substantiated by qualitative interview data drawn from a study I conducted on the process of consent as experienced by participants in clinical drug trials. (shrink)

: This paper examines the nature of the harm-benefit tradeoff in early clinical research for interventions that involve remote possibility of direct benefit and likelihood of direct harms to research participants with fatal prognoses, by drawing on the example of gene transfer trials for glioblastoma multiforme. We argue that the appeal made by the component approach to clinical equipoise fails to account fully for the nature of the harm-benefit tradeoff—individual harm for social benefit—that would be required to justify such research. (...) An analysis of what we label "collateral affective benefits," such as the experience of hope or exercise of altruism, shows that the existence of these motivations reinforces rather than mitigates the necessity of justification by reference to social benefit. Evaluations of social benefit must be taken seriously in the research ethics review process to avoid the exploitation of research participants' motivations of hope or altruism and to avoid the possibility of inadvertent exploitation of high-risk research participants and the harms that would associate with such exploitation. (shrink)

Institutional review boards and investigators are used to talking about risks of harm. Both low risks of great harm and high risks of small harm must be disclosed to prospective subjects and should be explained and categorized in ways that help potential subjects to understand and weigh them appropriately. Everyone on an IRB has probably spent time at meetings arguing over whether a three-page bulleted list of risk description is helpful or overkill for prospective subjects. Yet only a small fraction (...) of all the time and attention lavished on risk disclosure has been devoted to discussing whether and when potential benefit to subjects can reasonably be claimed and, if so, how it should be described in the consent form and process.Traditionally, IRBs and regulators have worked to ensure that clear lines can be drawn between research that, by definition, carries no potential for direct benefit — because it uses healthy volunteers or because it is not foreseeably focused on the development of treatments — and research that does have the development of effective treatments as its goal. (shrink)